MSC Detailed Report

Therapeutic Area		immunity
Rank		1
Score		0.772
Probiotic Score		0.998

Organism		Lacticaseibacillus paracasei
Lineage		d__Bacteria;p__Bacillota;c__Bacilli;o__Lactobacillales;f__Lactobacillaceae;g__Lacticaseibacillus;s__Lacticaseibacillus paracasei
Closest Reference Strain		Lacticaseibacillus paracasei JCM 8130
Warning		nan

Assembly QC

Completeness	Contamination
99.83	0.01

Assembly Metric

Metric	Value
# contigs (>= 0 bp)	3
# contigs (>= 1000 bp)	3
# contigs (>= 5000 bp)	3
# contigs (>= 10000 bp)	3
# contigs (>= 25000 bp)	2
# contigs (>= 50000 bp)	2
Total length (>= 0 bp)	3025352
Total length (>= 1000 bp)	3025352
Total length (>= 5000 bp)	3025352
Total length (>= 10000 bp)	3025352
Total length (>= 25000 bp)	3001145
Total length (>= 50000 bp)	3001145
# contigs	3
Largest contig	2939026
Total length	3025352
GC (%)	46
N50	2939026
N75	2939026
L50	1
L75	1
# N's per 100 kbp	0

Genome Characterization

COGID	COGDescription	COGCount	COGPercentage
C	[C] Energy production and conversion	115	4.55
D	[D] Cell cycle control, cell division, and chromosome partitioning	37	1.46
E	[E] Amino acid transport and metabolism	199	7.88
F	[F] Nucleotide transport and metabolism	110	4.35
G	[G] Carbohydrate transport and metabolism	269	10.65
H	[H] Coenzyme transport and metabolism	61	2.41
I	[I] Lipid transport and metabolism	59	2.34
J	[J] Translation, ribosomal structure, and biogenesis	166	6.57
K	[K] Transcription	239	9.46
L	[L] Replication, recombination, and repair	184	7.28
M	[M] Cell wall/membrane/envelope biogenesis	130	5.15
N	[N] Cell motility	8	0.32
O	[O] Post-translational modification, protein turnover, and chaperones	56	2.22
P	[P] Inorganic ion transport and metabolism	148	5.86
Q	[Q] Secondary metabolites biosynthesis, transport, and catabolism	30	1.19
S	[S] Function unknown	525	20.78
T	[T] Signal transduction mechanisms	61	2.41
U	[U] Intracellular trafficking, secretion, and vesicular transport	44	1.74
V	[V] Defense mechanisms	85	3.37

SEQUENCE	START	END	STRAND	GENE	Description	RESISTANCE

SEQUENCE	START	END	STRAND	GENE	Description

Features	Counts
contigs	3
bases	3025352
CDS	2901
gene	3010
misc_RNA	33
rRNA	15
repeat_region	1
tRNA	60
tmRNA	1

34847891 Due to the importance of using cost-effective methods for therapeutic purposes, the function of probiotics as safe microorganisms and the study of their relevant functional mechanisms have recently been in the spotlight. Finding the mechanisms of attachment and stability and their beneficial effects on the immune system can be useful in identifying and increasing the therapeutic effects of probiotics. In this review, the functional mechanisms of probiotics were comprehensively investigated. Relevant articles were searched in scientific sources, documents, and databases, including PubMed, NCBI, Bactibace, OptiBac, and Bagel4. The most important functional mechanisms of probiotics and their effects on strengthening the epithelial barrier, competitive inhibition of pathogenic microorganisms, production of antimicrobials, binding and interaction with the host, and regulatory effects on the immune system were discussed.In this regard, the attachment of probiotics to the epithelium is very important because the prerequisite for their proper functioning is to establish a proper connection to the epithelium. Therefore, more attention should be paid to the binding effect of probiotics, including sortase A, a significant factor involved in the expression of sortase-dependent proteins (SDP), on their surface as mediators of intestinal epithelial cell binding. In general, by investigating the functional mechanisms of probiotics, it was concluded that the mechanism by which probiotics regulate the immune system and adhesion capacity can directly and indirectly have preventive and therapeutic effects on a wide range of diseases. However, further study of these mechanisms requires extensive research on various aspects.

32328062 Studies have demonstrated that lipoteichoic acid (LTA) is involved in the immunomodulatory properties of some immunobiotic lactobacilli. The aim of this work was to evaluate whether LTA contributes to the capacity of Lactobacillus plantarum CRL1506 in modulating the intestinal innate antiviral immune response. A D-alanyl-lipoteichoic acid biosynthesis protein (dltD) knockout CRL1506 strain (L. plantarumΔdltD) was obtained, and its ability to modulate Toll-like receptor (TLR)-3-mediated immune response was evaluated in vitro in porcine intestinal epithelial (PIE) cells and in vivo in Balb/c mice. Wild-type (WT) CRL1506 (L. plantarum WT) was used as positive control. The challenge of PIE cells with the TLR3 agonist poly(I:C) significantly increased interferon (IFN)-β, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 expressions. PIE cells pretreated with L. plantarumΔdltD or L. plantarum WT showed higher levels of IFN-β while only L. plantarum WT significantly reduced the expression of IL-6 and MCP-1 when compared with poly(I:C)-treated control cells. The oral administration of L. plantarum WT to mice prior the intraperitoneal injection of poly(I:C) significantly increased IFN-β and IL-10 and reduced intraepithelial lymphocytes (CD3+NK1.1+CD8αα+) and pro-inflammatory mediators (TNF-α, IL-6, and IL-15) in the intestinal mucosa. Similar to the WT strain, L. plantarumΔdltD-treated mice showed enhanced levels of IFN-β after poly(I:C) challenge. However, treatment of mice with L. plantarumΔdltD was not able to increase IL-10 or reduce CD3+NK1.1+CD8αα+ cells, TNF-α, IL-6, or IL-15 in the intestine. These results indicate that LTA would be a key molecule in the anti-inflammatory effect induced by the CRL1506 strain in the context of TLR3-mediated inflammation.

17434999 Lipoteichoic acid (LTA) is a macroamphiphile molecule which performs several functions in gram-positive bacteria, such as maintenance of cell wall homeostasis. D-alanylation of LTA requires the proteins encoded by the dlt operon, and this process is directly related to the charge properties of this polymer strongly contributing to its function. The insertional inactivation of dltD of the probiotic strain Lactobacillus rhamnosus GG (ATCC 53103) resulted in the complete absence of D-alanyl esters in the LTA as confirmed by nuclear magnetic resonance analysis. This was reflected in modifications of the bacterial cell surface properties. The dltD strain showed 2.4-fold-increased cell length, a low survival capacity in response to gastric juice challenge, an increased sensitivity to human beta-defensin-2, an increased rate of autolysis, an increased capacity to initiate growth in the presence of an anionic detergent, and a decreased capacity to initiate growth in the presence of cationic peptides compared to wild-type results. However, in vitro experiments revealed no major differences for adhesion to human intestinal epithelial cells, biofilm formation, and immunomodulation. These properties are considered to be important for probiotics. The role of the dlt operon in lactobacilli is discussed in view of these results.

32585269 Exopolysaccharides (EPS) are extracellular macromolecules excreted as tightly bound capsule or loosely attached slime layer in microorganisms. They play most prominent role against desiccation, phagocytosis, cell recognition, phage attack, antibiotics or toxic compounds and osmotic stress. In the last few decades, natural polymers have gained much attention among scientific communities owing to their therapeutic potential. In particular the EPS retrieved from probiotic bacteria with varied carbohydrate compositions possess a plenty of beneficial properties. Different probiotic microbes have unique behavior in expressing their capability to display significant health promoting characteristics in the form of polysaccharides. In this new era of alternative medicines, these polysaccharides are considered as substitutes for synthetic drugs. The EPS finds applications in various fields like textiles, cosmetics, bioremediation, food and therapeutics. The present review is focused on sources, chemical composition, biosynthetic pathways of EPS and their biological potential. More attention has been given to the scientific investigations on antimicrobial, antitumor, anti-biofilm, antiviral, anti-inflammatory and immunomodulatory activities.

25186587 Lactobacillus rhamnosus GG (LGG) is one of the most widely used probiotic strains. Various health effects are well documented including the prevention and treatment of gastro-intestinal infections and diarrhea, and stimulation of immune responses that promote vaccination or even prevent certain allergic symptoms. However, not all intervention studies could show a clinical benefit and even for the same conditions, the results are not univocal. Clearly, the host phenotype governed by age, genetics and environmental factors such as the endogenous microbiota, plays a role in whether individuals are responders or non-responders. However, we believe that a detailed knowledge of the bacterial physiology and the LGG molecules that play a key role in its host-interaction capacity is crucial for a better understanding of its potential health benefits. Molecules that were yet identified as important factors governing host interactions include its adhesive pili or fimbriae, its lipoteichoic acid molecules, its major secreted proteins and its galactose-rich exopolysaccharides, as well as specific DNA motifs. Nevertheless, future studies are needed to correlate specific health effects to these molecular effectors in LGG, and also in other probiotic strains.

17954723 To define the role of lipoteichoic acid (LTA) in innate immunity to gram-positive bacteria, we investigated the production of tumor necrosis factor alpha (TNF-alpha) by macrophages stimulated with gram-positive bacterial culture supernatants (GPCSs) after their LTA was removed or inactivated. GPCSs were obtained from three gram-positive species (pneumococci, staphylococci, and group B streptococci) during the exponential growth phase (designated early GPCSs) or at the senescent stage (designated late GPCSs). LTA was removed using an anti-LTA antibody or was inactivated by alkaline hydrolysis or platelet-activating factor acetylhydrolase (PAF-AH) treatment. Both early and late GPCSs from the three gram-positive bacteria stimulated macrophages to produce TNF-alpha primarily via Toll-like receptor 2 (TLR2), although late pneumococcal supernatant could stimulate macrophages via TLR4 as well. Following LTA inactivation by both methods, early GPCS lost about 85 to 100% of its activity and late GPCS lost about 50 to 90%. Both early and late culture supernatants from Escherichia coli could be inactivated by alkali hydrolysis but not by PAF-AH. In addition, removal of LTA from an early staphylococcal culture supernatant with a monoclonal antibody reduced about 70 to 85% of its potency. Reconstitution of inactivated early GPCS with a highly purified LTA restored its inflammatory activity, but the restored GPCS had higher activity than the pure LTA alone. These findings indicate that LTA is the primary TLR2 ligand in the early phase of gram-positive bacterial infection and remains a major ligand in the late phase when another TLR2 and TLR4 ligand(s) appears. In addition, our findings suggest that another gram-positive bacterial factor(s) synergizes with LTA in inducing inflammatory responses.

19052326 Lactobacilli have been crucial for the production of fermented products for centuries. They are also members of the mutualistic microbiota present in the human gastrointestinal and urogenital tract. Recently, increasing attention has been given to their probiotic, health-promoting capacities. Many human intervention studies demonstrating health effects have been published. However, as not all studies resulted in positive outcomes, scientific interest arose regarding the precise mechanisms of action of probiotics. Many reported mechanistic studies have addressed mainly the host responses, with less attention being focused on the specificities of the bacterial partners, notwithstanding the completion of Lactobacillus genome sequencing projects, and increasing possibilities of genomics-based and dedicated mutant analyses. In this emerging and highly interdisciplinary field, microbiologists are facing the challenge of molecular characterization of probiotic traits. This review addresses the advances in the understanding of the probiotic-host interaction with a focus on the molecular microbiology of lactobacilli. Insight into the molecules and genes involved should contribute to a more judicious application of probiotic lactobacilli and to improved screening of novel potential probiotics.

27746766 The Bifidobacteria show great diversity in the cell surface architecture which may influence the physicochemical properties of the bacterial cell and strain specific properties. The immunomodulatory role of bifidobacteria has been extensively studied, however studies on the immunoreactivity of their protein molecules are very limited. Here, we compared six different methods of protein isolation and purification and we report identification of immunogenic and immunoreactive protein of two human Bifidobacterium longum ssp. longum strains. We evaluated potential immunoreactive properties of proteins employing polyclonal sera obtained from germ free mouse, rabbit and human. The protein yield was isolation method-dependent and the reactivity of proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and have them sequenced. Among the immunoreactive proteins we identified enolase, aspartokinase, pyruvate kinase, DnaK (B. longum ssp. longum CCM 7952) and sugar ABC transporter ATP-binding protein, phosphoglycerate kinase, peptidoglycan synthethase penicillin-binding protein 3, transaldolase, ribosomal proteins and glyceraldehyde 3-phosphate dehydrogenase (B. longum ssp. longum CCDM 372).

21897224 PURPOSE OF REVIEW: The beneficial effects of probiotics have been demonstrated in many diseases. One of the major mechanisms of probiotic action is through the regulation of host immune response. This review highlights the recent scientific research findings that advance our understanding of probiotic regulation of the host immune response with potential application for disease prevention and treatment.

30275399 Members of the genus Bifidobacterium are found in a wide-range of habitats and are used as important probiotics. Thus, exploration of their functional traits at the genus level is of utmost significance. Besides, this genus has been demonstrated to exhibit an open pan-genome based on the limited number of genomes used in earlier studies. However, the number of genomes is a crucial factor for pan-genome calculations. We have analyzed the pan-genome of a comparatively larger dataset of 215 members of the genus Bifidobacterium belonging to different habitats, which revealed an open nature. The pan-genome for the 56 probiotic and human-gut strains of this genus, was also found to be open. The accessory- and unique-components of this pan-genome were found to be under the operation of Darwinian selection pressure. Further, their genome-size variation was predicted to be attributed to the abundance of certain functions carried by genomic islands, which are facilitated by insertion elements and prophages. In silico functional and host-microbe interaction analyses of their core-genome revealed significant genomic factors for niche-specific adaptations and probiotic traits. The core survival traits include stress tolerance, biofilm formation, nutrient transport, and Sec-secretion system, whereas the core probiotic traits are imparted by the factors involved in carbohydrate- and protein-metabolism and host-immunomodulations.

18631181 The group of exported proteins of a bacterium are those proteins that are sorted from the cytoplasm to the bacterial surface or to the surroundings of the microorganism. In probiotic bacteria, these proteins are of special relevance because they might determine important traits such as adhesion to intestinal surfaces and molecular cross-talking with the host. Current knowledge about the presence and biological relevance of exported proteins produced by the main genera of probiotic bacteria in the gastrointestinal environment is reviewed in this minireview. As will be seen, some of these proteins are involved in host adhesion or are able to modify certain signalization pathways within host cells, whereas others are important for the physiology of probiotic bacteria in the gastrointestinal tract.

29859262 Spore forming Bacillus species are widely used as probiotics for human dietary supplements and in animal feeds. However, information on genetic basis of their probiotic action is obscure. Therefore, the present investigation was undertaken to elucidate probiotic traits of B. coagulans HS243 through its genome analysis. Genome mining revealed the presence of an arsenal of marker genes attributed to genuine probiotic traits. In silico analysis of HS243 genome revealed the presence of multi subunit ATPases, ADI pathway genes, chologlycine hydrolase, adhesion proteins for surviving and colonizing harsh gastric transit. HS243 genome harbored vitamin and essential amino acid biosynthetic genes, suggesting the use of HS243 as a nutrient supplement. Bacteriocin producing genes highlighted the disease preventing potential of HS243. Thus, this work established that HS243 possessed the genetic repertoire required for surviving harsh gastric transit and conferring health benefits to the host which were further validated by wet lab evidences.

35024559 Probiotic strains from different origins have shown promise in recent decades for their health benefits, for example in promoting and regulating the immune system. The immunomodulatory potential of four Lactobacillus strains from animal and plant origins was evaluated in this paper based on their genomic information. Comparative genomic analysis was performed through genome alignment, average nucleotide identity (ANI) analysis and gene mining for putative immunomodulatory genes. The genomes of the four Lactobacillus strains show relative similarities in multiple regions, as observed in the genome alignment. However, ANI analysis showed that L. mucosae LM1 and L. fermentum SK152 are the most similar when considering their nucleotide sequences alone. Gene mining of putative immunomodulatory genes studied from L. plantarum WCFS1 yielded multiple results in the four potential probiotic strains, with L. plantarum SK151 showing the largest number of genes at around 74 hits, followed by L. johnsonii PF01 at 41 genes when adjusted for matches with at least 30 % identity. Looking at the immunomodulatory genes in each strain, L. plantarum SK151 and L. johnsonii PF01 may have wider activity, covering both immune activation and immune suppression, as compared to L. mucosae LM1 and L. fermentum SK152, which could be more effective in activating immune cells and the pro-inflammatory cascade rather than suppressing it. The similarities and differences between the four Lactobacillus species showed that there is no definitive trend based on the origin of isolation alone. Moreover, higher percentage identities between genomes do not directly correlate with higher similarities in potential activity, such as in immunomodulation. The immunomodulatory function of each of the four Lactobacillus strains should be observed and verified experimentally in the future, since some the activity of some genes may be strain-specific, which would not be identified through comparative genomics alone.

16368998 Heat shock proteins of the GroEL or Hsp60 class are highly conserved proteins essential to all living organisms. Even though GroEL proteins are classically considered intracellular proteins, they have been found at the surface of several mucosal pathogens and have been implicated in cell attachment and immune modulation. The purpose of the present study was to investigate the GroEL protein of a gram-positive probiotic bacterium, Lactobacillus johnsonii La1 (NCC 533). Its presence at the bacterial surface was demonstrated using a whole-cell enzyme-linked immunosorbent assay and could be detected in bacterial spent culture medium by immunoblotting. To assess binding of La1 GroEL to mucins and intestinal epithelial cells, the La1 GroEL protein was expressed in Escherichia coli. We report here that La1 recombinant GroEL (rGroEL) binds to mucins and epithelial cells and that this binding is pH dependent. Immunomodulation studies showed that La1 rGroEL stimulates interleukin-8 secretion in macrophages and HT29 cells in a CD14-dependent mechanism. This property is common to rGroEL from other gram-positive bacteria but not to the rGroEL of the gastric pathogen Helicobacter pylori. In addition, La1 rGroEL mediates the aggregation of H. pylori but not that of other intestinal pathogens. Our in vitro results suggest that GroEL proteins from La1 and other lactic acid bacteria might play a role in gastrointestinal homeostasis due to their ability to bind to components of the gastrointestinal mucosa and to aggregate H. pylori.

28491143 There is a growing concern about the increase in human morbidity and mortality caused by foodborne pathogens. Antibiotics were and still are used as the first line of defense against these pathogens, but an increase in the development of bacterial antibiotic resistance has led to a need for alternative effective interventions. Probiotics are used as dietary supplements to promote gut health and for prevention or alleviation of enteric infections. They are currently used as generics, thus making them non-specific for different pathogens. A good understanding of the infection cycle of the foodborne pathogens as well as the virulence factors involved in causing an infection can offer an alternative treatment with specificity. This specificity is attained through the bioengineering of probiotics, a process by which the specific gene of a pathogen is incorporated into the probiotic. Such a process will subsequently result in the inhibition of the pathogen and hence its infection. Recombinant probiotics offer an alternative novel therapeutic approach in the treatment of foodborne infections. This review article focuses on various strategies of bioengineered probiotics, their successes, failures and potential future prospects for their applications.

25500495 Surface proteins of probiotic microbes, including Lactobacillus acidophilus and Lactobacillus gasseri, are believed to promote retention in the gut and mediate host-bacterial communications. Sortase, an enzyme that covalently couples a subset of extracellular proteins containing an LPXTG motif to the cell surface, is of particular interest in characterizing bacterial adherence and communication with the mucosal immune system. A sortase gene, srtA, was identified in L. acidophilus NCFM (LBA1244) and L. gasseri ATCC 33323 (LGAS_0825). Additionally, eight and six intact sortase-dependent proteins were predicted in L. acidophilus and L. gasseri, respectively. Due to the role of sortase in coupling these proteins to the cell wall, ΔsrtA deletion mutants of L. acidophilus and L. gasseri were created using the upp-based counterselective gene replacement system. Inactivation of sortase did not cause significant alteration in growth or survival in simulated gastrointestinal juices. Meanwhile, both ΔsrtA mutants showed decreased adhesion to porcine mucin in vitro. Murine dendritic cells exposed to the ΔsrtA mutant of L. acidophilus or L. gasseri induced lower levels of pro-inflammatory cytokines TNF-α and IL-12, respectively, compared with the parent strains. In vivo co-colonization of the L. acidophilus ΔsrtA mutant and its parent strain in germ-free 129S6/SvEv mice resulted in a significant one-log reduction of the ΔsrtA mutant population. Additionally, a similar reduction of the ΔsrtA mutant was observed in the caecum. This study shows for the first time that sortase-dependent proteins contribute to gut retention of probiotic microbes in the gastrointestinal tract.

36033850 Viral infections are a major cause of severe, fatal diseases worldwide. Recently, these infections have increased due to demanding contextual circumstances, such as environmental changes, increased migration of people and product distribution, rapid demographic changes, and outbreaks of novel viruses, including the COVID-19 outbreak. Internal variables that influence viral immunity have received attention along with these external causes to avert such novel viral outbreaks. The gastrointestinal microbiome (GIM), particularly the present probiotics, plays a vital role in the host immune system by mediating host protective immunity and acting as an immune regulator. Bacteriocins possess numerous health benefits and exhibit antagonistic activity against enteric pathogens and immunobiotics, thereby inhibiting viral infections. Moreover, disrupting the homeostasis of the GIM/host immune system negatively affects viral immunity. The interactions between bacteriocins and infectious viruses, particularly in COVID-19, through improved host immunity and physiology are complex and have not yet been studied, although several studies have proven that bacteriocins influence the outcomes of viral infections. However, the complex transmission to the affected sites and siRNA defense against nuclease digestion lead to challenging clinical trials. Additionally, bacteriocins are well known for their biofunctional properties and underlying mechanisms in the treatment of bacterial and fungal infections. However, few studies have shown the role of probiotics-derived bacteriocin against viral infections. Thus, based on the results of the previous studies, this review lays out a road map for future studies on bacteriocins for treating viral infections.

32849426 Bacterial lipoproteins are well-recognized microorganism-associated molecular patterns, which interact with Toll-like receptor (TLR) 2, an important pattern recognition receptor of the host innate immune system. Lipoproteins are conjugated with two- or three-acyl chains (di- or tri-acyl), which is essential for appropriate anchoring in the cell membrane as well as for the interaction with TLR2. Lipoproteins have mostly been studied in pathogens and have established roles in various biological processes, such as nutrient import, cell wall cross-linking and remodeling, and host-cell interaction. By contrast, information on the role of lipoproteins in the physiology and host interaction of probiotic bacteria is scarce. By deletion of lgt, encoding prolipoprotein diacylglyceryl transferase, responsible for lipidation of lipoprotein precursors, we investigated the roles of the collective group of lipoproteins in the physiology of the probiotic model strain Lactobacillus plantarum WCFS1 using proteomic analysis of secreted proteins. To investigate the consequences of the lgt mutation in host-cell interaction, the capacity of mutant and wild-type bacteria to stimulate TLR2 signaling and inflammatory responses was compared using (reporter-) cell-based models. These experiments exemplified the critical contribution of the acyl chains of lipoproteins in immunomodulation. To the best of our knowledge, this is the first study that investigated collective lipoprotein functions in a model strain for probiotic lactobacilli, and we show that the lipoproteins in L. plantarum WCFS1 are critical drivers of anti-inflammatory host responses toward this strain.

20017931 BACKGROUND: Many Gram-positive lactic acid bacteria (LAB) produce anti-bacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. These peptides fall structurally into three different classes, I, II, III, with class IIa being pediocin-like single entities and class IIb being two-peptide bacteriocins. Self-protective cognate immunity proteins are usually co-transcribed with these toxins. Several examples of cognates for IIa have already been solved structurally. Streptococcus pyogenes, closely related to LAB, is one of the most common human pathogens, so knowledge of how it competes against other LAB species is likely to prove invaluable.

36211408 Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to the development of allergic asthma in childhood. Proline metabolism could be a well target for the prevention of allergic asthma in childhood.

35591998 ['The gut microbiome engages in constant interactions with the immune system, laying down the fundamentals of what we perceive as health or disease. The gut microbiota acts locally in the intestines and distally in other organs, such as the lungs. This influence (termed "the gut-lung axis") constitutes the basis for harnessing the microbiome to prevent or treat chronic respiratory diseases. Within this context, two approaches gained the most attention: the diet interventions (which shape the microbiome) and the probiotics (which exert beneficial effects directly on the host). Microbial products, which constitute a means of communication along the gut-lung axis, are only now emerging as a new class of potential therapeutics. Here, we provide a comprehensive overview of microbial products active in the airways, describe the immunological mechanisms they trigger, and discuss their clinical advantages and pitfalls.']

33567701 The aim of this study was to investigate the effects of 24-week synbiotic supplementation on chronic inflammation and the gut microbiota in obese patients with type 2 diabetes. We randomized 88 obese patients with type 2 diabetes to one of two groups for 24 weeks: control or synbiotic (Lacticaseibacillus paracasei strain Shirota (previously Lactobacillus casei strain Shirota) and Bifidobacterium breve strain Yakult, and galactooligosaccharides). The primary endpoint was the change in interleukin-6 from baseline to 24 weeks. Secondary endpoints were evaluation of the gut microbiota in feces and blood, fecal organic acids, high-sensitivity C-reactive protein, lipopolysaccharide-binding protein, and glycemic control. Synbiotic administration for 24 weeks did not significantly affect changes in interleukin-6 from baseline to 24 weeks (0.35 ± 1.99 vs. -0.24 ± 1.75 pg/mL, respectively). Relative to baseline, however, at 24 weeks after synbiotic administration there were positive changes in the counts of Bifidobacterium and total lactobacilli, the relative abundances of Bifidobacterium species such as Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and the concentrations of acetic and butyric acids in feces. No significant changes in inflammatory markers were found in the synbiotic group compared to the control group. However, synbiotic administration at least partially improved the gut environment in obese patients with type 2 diabetes.

28561762 The aim of this study was to investigate the impact of consuming dairy yogurt containing Lactobacillus paracasei ssp. paracasei (L. paracasei), Bifidobacterium animalis ssp. lactis (B. lactis) and heat-treated Lactobacillus plantarum (L. plantarum) on immune function. A randomized, open-label, placebo-controlled study was conducted on 200 nondiabetic subjects. Over a twelve-week period, the test group consumed dairy yogurt containing probiotics each day, whereas the placebo group consumed milk. Natural killer (NK) cell activity, interleukin (IL)-12 and immunoglobulin (Ig) G1 levels were significantly increased in the test group at twelve weeks compared to baseline. Additionally, the test group had significantly greater increases in serum NK cell activity and interferon (IFN)-γ and IgG1 than placebo group. Daily consumption of dairy yogurt containing L. paracasei, B. lactis and heat-treated L. plantarum could be an effective option to improve immune function by enhancing NK cell function and IFN-γ concentration (ClinicalTrials.gov: NCT03051425).

29277839 BACKGROUND/OBJECTIVES: Cystic fibrosis (CF) is characterized by excessive activation of immune processes. The aim of this study was to evaluate the effect of synbiotic supplementation on the inflammatory response in children/adolescents with CF.

31328382 BACKGROUND: The mechanisms of downregulation of protective immunity against Helicobacter pylori (Hp) infection strongly depend on dendritic cell (DC)-induced T-lymphocyte differentiation pattern. Lactic acid bacteria (LAB) strains can modulate Hp-induced immunoresponse by changes in DC activation profiles. Here, we want to find out if the LAB-pulsed DCs will change Hp-induced T-cell responsiveness patterns.

35664846 In the recent years, safety concerns regarding the administration of probiotics led to an increased interest in developing inactivated probiotics, also called "paraprobiotics". Gamma irradiation represents a promising tool that can be used to produce safe paraprobiotics by inhibiting replication while preserving the structure, the metabolic activity, and the immunogenicity of bacteria. In this study, we evaluated the ability of four strains of lactic acid bacteria (LAB: Lacticaseibacillus casei, Lactobacillus acidophilus, Lactiplantibacillus plantarum, and Lacticaseibacillus paracasei) in preserving the metabolic activity and the immune modulation of swine porcine peripheral blood mononuclear cells, after gamma irradiation or heat inactivation. Our results show that all four strains retained the metabolic activity following gamma irradiation but not after heat inactivation. In terms of immune-modulatory capacity, irradiated L. acidophilus and Lc. paracasei were able to maintain an overall gene expression pattern similar to their live state, as heat inactivation did with Lc. casei. Moreover, we show that the two inactivation methods applied to the same strain can induce an opposed expression of key genes involved in pro-inflammatory response (e.g., IFNα and interleukin-6 for Lc. casei), whereas gamma irradiation of L. acidophilus and Lc. paracasei was able to induce a downregulation of the anti-inflammatory TGFβ. Taken together, our data show that immune modulation can be impacted not only by different inactivation methods but also by the strain of LAB selected. This study highlights that gamma irradiation harbors the potential to produce safe non-replicative metabolically active LAB and identifies immunomodulatory capacities that may be applied as vaccine adjuvants.

31426284 Allergic disease is one of the most important and common health problems worldwide. We have previously demonstrated that a fig leaf-derived lactic acid bacterium Lactobacillus (Lb.) paracasei IJH-SONE68 produces a novel exopolysaccharide (EPS). Furthermore, we have shown that the EPS inhibits the catalytic activity of hyaluronidase (EC 3.2.1.36) promoting inflammatory reactions. To evaluate the anti-allergy and anti-inflammatory effects of the EPS, in the present study, we employed the picryl-chloride-induced delayed-type (type IV) allergy model mice, which is used to evaluate the contact dermatitis. Oral administration of the EPS was observed to reduce the ear swelling in the model mice. We also observed that the overexpression of ear interleukin-4 (T helper (Th) 2 cytokine) mRNA and the increase in serum immunoglobulin E (IgE) are repressed. However, the expression of interferon-γ (Th1 cytokine) was not accelerated in all of the allergen-challenged model mice. The improvement may be responsible for the Th2 downregulation rather than the Th1 upregulation. In addition, the symptom of immediate-type (type I) allergy model mice was improved by oral administration of the IJH-SONE68 cell (data not shown). We can conclude that the IJH-SONE68-derived EPS is useful to improve the type I and IV allergies including atopic dermatitis.

32638482 AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system.

32804985 A strain of lactic acid bacteria, Lactobacillus paracasei KW3110 (KW3110), activates M2 macrophages with anti-inflammatory reactions and mitigates aging-related chronic inflammation and blue-light exposure-induced retinal inflammation in mice. However, the mechanism underlying the anti-inflammatory effects of KW3110 remains unclear. In this study, we investigated the anti-inflammatory effects of KW3110 using both mouse and human immune cells and evaluated the suppressive effect of KW3110 on the inflammatory reactions of the cells stimulated with lipopolysaccharide and adenosine 5'-triphosphate (LPS/ATP). KW3110 treatment induced anti-inflammatory cytokine interleukin (IL)-10 production in the supernatants of murine macrophage-like cells, J774A.1, and suppressed IL-1β production in the supernatants of LPS/ATP-stimulated cells. The influence of KW3110 on the production of these cytokines was inhibited by pre-treatment with phagocytosis blocker or transfection with siRNAs for IL-10 signaling components. KW3110 treatment also suppressed activation of caspase-1, an active component of inflammasome complexes, in LPS/ATP-stimulated J774A.1 cells, and its effect was inhibited by transfection with siRNAs for IL-10 signaling components. In addition to the effects of KW3110 on J774A.1 cells, KW3110 treatment induced IL-10 production in the supernatants of human monocytes, and KW3110 or IL-10 treatment suppressed caspase-1 activation and IL-1β production in the supernatants of LPS/ATP-stimulated cells. These results suggest that KW3110 suppresses LPS/ATP stimulation-induced caspase-1 activation and IL-1β production by promoting IL-10 production in mouse and human immune cells. Our findings reveal a novel anti-inflammatory mechanism of LAB and the effect of KW3110 on caspase-1 activation is expected to contribute to constructing future preventive strategies for inflammation-related disorders using food ingredients.

27294391 High contamination by aflatoxin B1 (AFB1) has been detected in Beja province (Tunisia) in many dairy products and animal feed, which has resulted in many tons of cereals and cereals being removed from the market, causing economic loss. While removal represents a means of reducing risk, exposures still occur. Studies have increasingly focused on means of AFB1 biodegradation/elimination using lactic acid bacteria and clay mineral. In the study here, Lactobacillus paracasei BEJ01 (LP) and montmorilonite clay (MT) were used to reduce the physio-/immunotoxicologic disorders that could develop in rats that underwent AFB1 exposures for a total of 7 consecutive days. The results indicated that rats treated with AFB1 (80 μg/kg BW) alone had significant decreases in lymphocytes in their blood (including B-lymphocytes, CD3(+), CD4(+), and CD8(+) T-lymphocyte subtypes, and NK cells), immunoglobulins (IgA and IgG) and pro-inflammatory cytokines; these rats also had altered oxidative stress status. In contrast, in rats treated with LP + MT (2 × 10(9) cfu/ml ∼ 2 mg/kg + 0.5 mg MT/kg BW) for a total of 7 days before, concurrent with or after AFB1 treatment, there was a significant blockade/mitigation of each AFB1-impacted parameter. Moreover, treatment with the mixture at any point in relation to AFB1 treatment expectedly caused enhanced TNFα and IL-1β expression relative to control values; all other parameters were comparable to values noted in control rats. Alone, the mixture had no impact on host parameters. From the results here it may be concluded the the LP + MT mixture was effective in protecting these hosts against AFB1-induced immunologic/physiologic disorders and that LP + MT could prevent and/or mitigate AFB1 toxicities in vivo.

28801270 Due to the growing number of multi-resistant Candida spp., adjuvant treatments that may help combat these fungal pathogens are relevant and useful. This study evaluated the immunomodulation and anti-Candida activity of Lactobacillus rhamnosus (LR), Lactobacillus acidophilus and Lactobacillus paracasei suspensions, either single- or multiple-strain, in mouse macrophages (RAW 264.7) and Galleria mellonella (GM). Mouse macrophages were activated by different lactobacilli suspensions and challenged with C. albicans (CA). Tumor necrosis factor (TNF)-α, interleukin IL-1β, IL-6 and IL-17 production and cell viability were investigated. LR was the best suspension for stimulating all evaluated cytokines and thus was used in subsequent in vivo assays. Two C. albicans clinical strains, CA21 and CA60, were then added to the GM assays to further confirm the results. LR suspension was injected into the larvae 24 h before challenging with CA. Survival curve, CFU per larva and hemocytes were counted. In the GM, the LR suspension increased the survival rate and hemocyte counts and decreased the CFU per larva counts for all groups. Lactobacilli suspensions presented strain-dependent immunomodulation; however, single suspensions showed better results. Anti-Candida activity was demonstrated by decreased Candida counts in the GM with the use of LR.

27913418 Lactobacillus paracasei DG is a bacterial strain with recognized probiotic properties and is used in commercial probiotic products. However, the mechanisms underlying its probiotic properties are mainly unknown. In this study, we tested the hypothesis that the ability of strain DG to interact with the host is at least partly associated with its ability to synthesize a surface-associated exopolysaccharide (EPS). Comparative genomics revealed the presence of putative EPS gene clusters in the DG genome; accordingly, EPS was isolated from the surface of the bacterium. A sample of the pure EPS from strain DG (DG-EPS), upon nuclear magnetic resonance (NMR) and chemical analyses, was shown to be a novel branched hetero-EPS with a repeat unit composed of l-rhamnose, d-galactose, and N-acetyl-d-galactosamine in a ratio of 4:1:1. Subsequently, we demonstrated that DG-EPS displays immunostimulating properties by enhancing the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), and particularly that of the chemokines IL-8 and CCL20, in the human monocytic cell line THP-1. In contrast, the expression of the cyclooxygenase enzyme COX-2 was not affected. In conclusion, DG-EPS is a bacterial macromolecule with the ability to boost the immune system either as a secreted molecule released from the bacterium or as a capsular envelope on the bacterial cell wall. This study provides additional information about the mechanisms supporting the cross talk between L. paracasei DG and the host.

28830549 BACKGROUND: Interleukin-22 (IL-22) plays a prominent role in epithelial regeneration and dampening of chronic inflammatory responses by protecting intestinal stem cells from immune-mediated tissue damage. IL-22 has a considerable therapeutic potential in graft-versus-host disease (GVHD), which is a frequent and challenging complication following allogeneic stem cell transplantation. The aim of our study was to engineer Lactobacillus for delivery of IL-22 directly to the intestinal mucosa as a new therapeutic strategy for GVHD.

30558320 Age-related macular degeneration and retinitis pigmentosa are leading causes of blindness and share a pathological feature, which is photoreceptor degeneration. To date, the lack of a potential treatment to prevent such diseases has raised great concern. Photoreceptor degeneration can be accelerated by excessive light exposure via an inflammatory response; therefore, anti-inflammatory agents would be candidates to prevent the progress of photoreceptor degeneration. We previously reported that a lactic acid bacterium, Lactobacillus paracasei KW3110 (L. paracasei KW3110), activated macrophages suppressing inflammation in mice and humans. Recently, we also showed that intake of L. paracasei KW3110 could mitigate visual display terminal (VDT) load-induced ocular disorders in humans. However, the biological mechanism of L. paracasei KW3110 to retain visual function remains unclear. In this study, we found that L. paracasei KW3110 activated M2 macrophages inducing anti-inflammatory cytokine interleukin-10 (IL-10) production in vitro using bone marrow-derived M2 macrophages. We also show that IL-10 gene expression was significantly increased in the intestinal immune tissues 6 h after oral administration of L. paracasei KW3110 in vivo. Furthermore, we demonstrated that intake of L. paracasei KW3110 suppressed inflammation and photoreceptor degeneration in a murine model of light-induced retinopathy. These results suggest that L. paracasei KW3110 may have a preventive effect against degrative retinal diseases.

35057558 The disturbance of intestinal microorganisms and the exacerbation of type 2 diabetes (T2D) are mutually influenced. In this study, the effect of exopolysaccharides (EPS) from Lactobacillus plantarum JY039 on the adhesion of Lactobacillus paracasei JY062 was investigated, as well as their preventive efficacy against T2D. The results showed that the EPS isolated from L. plantarum JY039 effectively improved the adhesion rate of L. paracasei JY062 to Caco-2 cells (1.8 times) and promoted the proliferation of L. paracasei JY062. In the mice experiment, EPS, L. paracasei JY062 and their complex altered the structure of the intestinal microbiota, which elevated the proportion of Bifidobacterium, Faecalibaculum, while inversely decreasing the proportion of Firmicutes, Muribaculaceae, Lachnospiraceae and other bacteria involved in energy metabolism (p < 0.01; p < 0.05); enhanced the intestinal barrier function; promoted secretion of the gut hormone peptide YY (PYY) and glucagon-like peptide-1 (GLP-1); and reduced inflammation by balancing pro-inflammatory factors IL-6, TNF-α and anti-inflammatory factor IL-10 (p < 0.01; p < 0.05). These results illustrate that EPS and L. paracasei JY062 have the synbiotic potential to prevent and alleviate T2D.

34605504 Inflammatory bowel disease (IBD) is a chronic intestinal inflammation that is currently incurable. Increasing evidence indicates that supplementation with probiotics could improve the symptoms of IBD. It is scientifically significant to identify novel and valid strains for treating IBD. It has been reported that the probiotic Lactobacillus paracasei L9 (L9), which is identified from the gut of healthy centenarians, can modulate host immunity and plays an anti-allergic role. Here, we demonstrated that L9 alleviates the pathological phenotypes of experimental colitis by expanding the abundance of butyrate-producing bacteria. Oral administration of sodium butyrate in experimental colitis recapitulates the L9 anti-inflammatory phenotypes. Mechanistically, sodium butyrate ameliorated the inflammatory responses by inhibiting the IL-6/STAT3 signaling pathway in colitis. Overall, these findings demonstrated that L9 alleviates the DSS-induced colitis development by enhancing the abundance of butyrate-producing bacterial strains that produce butyrate to suppress the IL-6/STAT3 signaling pathway, providing new insight into a promising therapeutic target for the remission of IBD.

34813868 In this study, we found that it is possible to screen Lactobacillus strains that enhance the immune function of mice using HCT-8 cells. Lactobacillus were co-incubated with intestinal epithelial HCT-8 cells to detect and screen the strains that induced more interleukin-6 (IL-6) in the culture supernatant. Simultaneously, a mouse model of low immunity was established to administer the screened lactobacilli by gavage. After 4 weeks of continuous gavage, related cytokines in blood and immune cell indexes in organs were detected to comprehensively evaluate the feasibility of in vitro cell culture model for screening immune-enhancing strains. The content of IL-6 in the culture supernatant of HCT-8 cells induced by the three tested strains increased approximately 5, 8 and 15 fold compared with that of the control group. IL-6 content in serum of mice was significantly higher than that of the control group provided with cyclophosphamide (CTX). Lactobacillus paracasei ZLPC01 presented a higher ability to protect against the immune damage of CTX by decreasing the serum IgG level, increasing the transformation of mouse splenocytes, and the activity of NK cells. Furthermore, L. paracasei ZLPC01 increased cytokine content in serum (IL-6, IL-2, TNF-α and IFN-γ) and colon (IL-6 and TNF-α) in CTX-treated mice. Screening strains that enhance immunity via an in vitro cell-line is simple in operation, and the results are well correlated with those of animal experiments, which is feasible and effective in practice. In addition, L. paracasei ZLPC01 could have the potential to enhance the immunity of mice effectively through inducing intestinal cells to produce IL-6, TNF-α and other cytokines.

36206543 The goal of this investigation was to find antidiabetic peptides and inhibit angiotensin converting enzyme (ACE) in Lacticaseibacillus paracasei (M11) fermented dromedary camel milk (Camelus dromedaries). According to the findings, the rate of antidiabetic activity increased along with the incubation periods and reached its peak after 48 hr of fermentation. The inhibitions of α-amylase, α-glucosidase, and lipase were 80.75, 59.62, and 65.46%, respectively. The inhibitory activity of ACE was 78.33%, and the proteolytic activity was 8.90 mg/mL. M11 at 0.25 mg/mL effectively suppressed LPS-induced pro-inflammatory cytokines and their mediators such as NO, TNF-α, IL-6, and IL-1β in RAW 264.7 cells. The rate of inoculum in the optimization phase was 1.5-2.5%, and the greatest proteolytic activity was observed after 48 hr of fermentation. The investigation of the above property in the ultrafiltered fermented milk exhibited the highest antidiabetic and ACE inhibition activities in the 3 kDa than 10 kDa fractions. The molecular weight was determined employing SDS-PAGE, and the six-peptide sequences were identified using 2D gel electrophoresis. Due to its high proteolytic activity, the L. paracasei strain has been reported to be useful in the production of ACE-inhibitory and antidiabetic peptides. Amino acid sequences such from ɑ1, ɑ2, and β-caseins have been identified within fermented camel milk by searching on online databases, including BIOPEP (for antidiabetic peptides) and AHTPDB (for hypertension peptides) to validate the antidiabetic and ACE-inhibitory actions of several peptides. PRACTICAL APPLICATIONS: The study aims to identify antidiabetic peptides and inhibit ACE in dromedary camel milk fermented with Lacticaseibacillus paracasei M11. Maximum antidiabetic and ACE-inhibitory actions of the fermented camel milk were observed in 3 kDa permeate fractions. Fermented camel milk significantly reduced the excessive TNF-α, IL-6, and IL-1β production in LPS-activated RAW 264.7 cells. RP-LC/MS was used to identify 6 bioactive peptides from dromedary fermented camel milk. This fermented camel milk could be used for the management of hypertension and diabetic related problems.

34113945 This study aimed to investigate the effects of probiotic Lactobacillus paracasei NL41 on inflammation and the gut microbiota of type 2 diabetic (T2D) rats induced by high-fat diet (HFD) and low-dose streptozotocin (STZ). A T2D rat model was established by inducing Sprague-Dawley rats with HFD/STZ, followed by 12-weeks L. paracasei NL41 gavage. The blood, colonic tissues, and feces samples of these rats were collected for inflammation, histology, and intestinal microbiota profiling. L. paracasei NL41 treatment induced remarkable improvement in the inflammatory status by decreasing the levels of serum lipopolysaccharides (LPS), free fatty acids (FFA), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-8 and increasing the level of IL-10. Gut barrier function was significantly protected in NL41-treated rats. Moreover, the strain NL41 induced changes in the microbiota structure and influenced the relative abundance of the key species. Specifically, Bacteroides, Clostridia (specifically, Ruminococcus torques), and Parasutterella were significantly reduced, while some beneficial microorganisms (Bacteroidales_S24-7_group and the families Lachnospiraceae and Ruminococcaceae) were enriched by NL41. The correlational analyses indicated that L. paracasei NL41 ameliorating inflammation was closely related to the key species of the gut microbiota. The present study indicates that probiotic L. paracasei NL41 decreases LPS-induced inflammation by improving the gut microbiota and preserving intestinal integrity.

36899903 Background: Probiotics may facilitate the clinical management of allergic diseases. However, their effects on allergic rhinitis (AR) remain unclear. We examined the efficacy and safety of Lacticaseibacillus paracasei GM-080 in a mouse model of airway hyper-responsiveness (AHR) and in children with perennial AR (PAR) by using a double-blind, prospective, randomized, placebo-controlled design. Methods: The production of interferon (IFN)-γ and interleukin (IL)-12 was measured by using an enzyme-linked immunosorbent assay. GM-080 safety was evaluated via the whole-genome sequencing (WGS) of virulence genes. An ovalbumin (OVA)-induced AHR mouse model was constructed, and lung inflammation was evaluated by measuring the infiltrating leukocyte content of bronchoalveolar lavage fluid. A clinical trial was conducted with 122 children with PAR who were randomized to receive different doses of GM-080 or the placebo for 3 months, and their AHR symptom severity scores, total nasal symptom scores (TNSSs), and Investigator Global Assessment Scale scores were examined. Results: Among the tested L. paracasei strains, GM-080 induced the highest IFN-γ and IL-12 levels in mouse splenocytes. WGS analysis revealed the absence of virulence factors or antibiotic-resistance genes in GM-080. The oral administration of GM-080 at 1 × 107 colony forming units (CFU)/mouse/day for 8 weeks alleviated OVA-induced AHR and reduced airway inflammation in mice. In children with PAR, the oral consumption of GM-080 at 2 × 109 CFU/day for 3 months ameliorated sneezing and improved Investigator Global Assessment Scale scores significantly. GM-080 consumption led to a nonsignificant decrease in TNSS and also nonsignificantly reduced IgE but increased INF-γ levels. Conclusion: GM-080 may be used as a nutrient supplement to alleviate airway allergic inflammation.

37002629 T cells play an important role in the development and progression of multiple sclerosis (MS), an autoimmune disease of the central nervous system. In the present study, the immunomodulatory impacts of two Lactobacillus strains, L paracasei DSM 13434 and L plantarum DSM 15312, on the frequency and cytokine production of CD4+ T cells in MS patients were explored. Thirty MS patients were enrolled in this study. The CD4+ T cells were isolated, cultured, and exposed to the media containing cell-free supernatants of L plantarum (group1), L paracasei (group 2), the mixture group of cell-free supernatants of both probiotics (group 3), and vehicle (control) group (group 4). The frequencies of T helper (Th) 1, Th17, Th2, and T regulatory type 1 (Tr1) cells and mean fluorescent intensity (MFI) of the associated cytokines were assessed using flow cytometry. The levels of interleukin 17 (IL-17), transforming growth factor β (TGF-β), and interferon-gamma (IFN-γ) cytokines in supernatants of all groups were measured by enzyme-linked immunosorbent assay. The percentage of Th1 cells and the MFI of IFN-γ in Th1 cells (CD4+ IFN-γ+) in all three probiotic treatment groups were significantly decreased compared to the control group. However, no significant changes were observed in the proportion and MFI of Th2, Th17, and Tr1 cells. A significant decrease was observed in IL-17 secretion in the supernatant of cultured CD4+ T cells in all three treatment groups in comparison with control. The levels of TGF-β and IFN-γ were not significantly different among any of the study groups. Collectively, cell-free supernatants of the lactobacilli showed an in vitro anti-inflammatory effect. However, further studies are needed to prove the real effects of probiotics on MS.

35395579 OBJECTIVES: Probiotics are gaining interest as alternative options for antibiotic or antiinflammatory drugs. Probiotics can affect the health of the host through metabolites and competitive inhibition adhesion of pathogenic microorganisms. Koumiss is an important part of the diet of Asian nomads, and is rich in a broad array of probiotics that can benefit the body. Mongolians have developed koumiss therapy to assist in the treatment of various diseases. In the present study, we investigate the beneficial effect of Lactobacillus paracasei, a strain isolated from koumiss, on a mouse model of diarrhea induced by Escherichia coli O8 (E. coli O8).

29065709 Cow's milk fermented with Lactobacillus paracasei CBA L74 (FM-CBAL74) exerts a preventive effect against infectious diseases in children. We evaluated if this effect is at least in part related to a direct modulation of non-immune and immune defence mechanisms in human enterocytes. Human enterocytes (Caco-2) were stimulated for 48 h with FM-CBAL74 at different concentrations. Cell growth was assessed by colorimetric assay; cell differentiation (assessed by lactase expression), tight junction proteins (zonula occludens1 and occludin), mucin 2, and toll-like receptor (TRL) pathways were analysed by real-time PCR; innate immunity peptide synthesis, beta-defensin-2 (HBD-2) and cathelicidin (LL-37) were evaluated by ELISA. Mucus layer thickness was analysed by histochemistry. FMCBA L74 stimulated cell growth and differentiation, tight junction proteins and mucin 2 expression, and mucus layer thickness in a dose-dependent fashion. A significant stimulation of HBD-2 and LL-37 synthesis, associated with a modulation of TLR pathway, was also observed. FM-CBAL74 regulates non-immune and immune defence mechanisms through a direct interaction with the enterocytes. These effects could be involved in the preventive action against infectious diseases demonstrated by this fermented product in children.

35630296 Hyperuricemia is a metabolic disorder caused by increased uric acid (UA) synthesis or decreased UA excretion. Changes in eating habits have led to an increase in the consumption of purine-rich foods, which is closely related to hyperuricemia. Therefore, decreased purine absorption, increased UA excretion, and decreased UA synthesis are the main strategies to ameliorate hyperuricemia. This study aimed to screen the lactic acid bacteria (LAB) with purine degrading ability and examine the serum UA-lowering effect in a hyperuricemia mouse model. As a result, Lacticaseibacillus paracasei MJM60396 was selected from 22 LAB isolated from fermented foods for 100% assimilation of inosine and guanosine. MJM60396 showed probiotic characteristics and safety properties. In the animal study, the serum uric acid was significantly reduced to a normal level after oral administration of MJM60396 for 3 weeks. The amount of xanthine oxidase, which catalyzes the formation of uric acid, decreased by 81%, and the transporters for excretion of urate were upregulated. Histopathological analysis showed that the damaged glomerulus, Bowman's capsule, and tubules of the kidney caused by hyperuricemia was relieved. In addition, the impaired intestinal barrier was recovered and the expression of tight junction proteins, ZO-1 and occludin, was increased. Analysis of the microbiome showed that the relative abundance of Muribaculaceae and Lachnospiraceae bacteria, which were related to the intestinal barrier integrity, was increased in the MJM60396 group. Therefore, these results demonstrated that L. paracasei MJM60396 can prevent hyperuricemia in multiple ways by absorbing purines, decreasing UA synthesis by suppressing xanthine oxidase, and increasing UA excretion by regulating urate transporters.

37049598 Intestinal epithelial barrier function is closely associated with the development of many intestinal diseases. Heat-killed Lacticaseibacillus paracasei (HK-LP) has been shown to improve intestinal health and enhance immunity. However, the function of HK-LP in the intestinal barrier is still unclear. This study characterized the inflammatory effects of seven HK-LP (1 μg/mL) on the intestinal barrier using lipopolysaccharide (LPS) (100 μg/mL)-induced Caco-2 cells. In this study, HK-LP 6105, 6115, and 6235 were selected, and their effects on the modulation of inflammatory factors and tight junction protein expression (claudin-1, zona occludens-1, and occludin) were compared. The effect of different cultivation times (18 and 48 h) was investigated in response to LPS-induced intestinal epithelial barrier dysfunction. Our results showed that HK-LP 6105, 6115, and 6235 improved LPS-induced intestinal barrier permeability reduction and transepithelial resistance. Furthermore, HK-LP 6105, 6115, and 6235 inhibited the pro-inflammatory factors (TNF-α, IL-1β, IL-6) and increased the expression of the anti-inflammatory factors (IL-4, IL-10, and TGF-β). HK-LP 6105, 6115, and 6235 ameliorated the inflammatory response. It inhibited the nuclear factor kappa B (NF-κB) signaling pathway-mediated myosin light chain (MLC)/MLC kinase signaling pathway by downregulating the Toll-like receptor 4 (TLR4)/NF-κB pathway. Thus, the results suggest that HK-LP 6150, 6115, and 6235 may improve intestinal health by regulating inflammation and TJ proteins. Postbiotics produced by these strains exhibit anti-inflammatory properties that can protect the intestinal barrier.

33016202 Administration of probiotics has been linked to immune regulation and changes in gut microbiota composition, with effects on atopic dermatitis (AD). In this study, we investigated amelioration of the symptoms of AD using Lactobacillus paracasei KBL382 isolated from the feces of healthy Koreans. Mice with Dermatophagoides farinae extract (DFE)-induced AD were fed 1 × 109 CFU d-1 of L. paracasei KBL382 for 4 weeks. Oral administration of L. paracasei KBL382 significantly reduced AD-associated skin lesions, epidermal thickening, serum levels of immunoglobulin E, and immune cell infiltration. L. paracasei KBL382-treated mice showed decreased production of T helper (Th)1-, Th2-, and Th17-type cytokines, including thymic stromal lymphopoietin, thymus, and activation-regulated chemokine, and macrophage-derived chemokine, and increased production of the anti-inflammatory cytokine IL-10 and transforming growth factor-β in skin tissue. Intake of L. paracasei KBL382 also increased the proportion of CD4+ CD25+ Foxp3+ regulatory T cells in mesenteric lymph nodes. In addition, administration of L. paracasei KBL382 dramatically changed the composition of gut microbiota in AD mice. Administration of KBL382 significantly ameliorates AD-like symptoms by regulating the immune response and altering the composition of gut microbiota.

36016576 Intense physical activity is often associated with undesirable physiological changes, including increased inflammation, transient immunodepression, increased susceptibility to infections, altered intestinal barrier integrity, and increased oxidative stress. Several trials suggested that probiotics supplementation may have beneficial effects on sport-associated gastro-intestinal and immune disorders. Recently, in a placebo-controlled human trial, the AminoAlta™ probiotic formulation (AApf) was demonstrated to increase the absorption of amino acids from pea protein, suggesting that the administration of AApf could overcome the compositional limitations of plant proteins. In this study, human cell line models were used to assess in vitro the potential capacity of AApf to protect from the physiological damages that an intense physical activity may cause. The obtained results revealed that the bacteria in the AApf have the ability to adhere to differentiated Caco-2 epithelial cell layer. In addition, the AApf was shown to reduce the activation of NF-κB in Caco-2 cells under inflammatory stimulation. Notably, this anti-inflammatory activity was enhanced in the presence of partially hydrolyzed plant proteins. The AApf also triggered the expression of cytokines by the THP-1 macrophage model in a dose-dependent manner. In particular, the expression of cytokines IL-1β, IL-6, and TNF-α was higher than that of the regulatory cytokine IL-10, resembling a cytokine profile characteristic of M1 phenotype, which typically intervene in counteracting bacterial and viral infections. Finally, AApf was shown to reduce transepithelial permeability and increase superoxide dismutase activity in the Caco-2 cell model. In conclusion, this study suggests that the AApf may potentially provide a spectrum of benefits useful to dampen the gastro-intestinal and immune detrimental consequences of an intense physical activity.

37114144 In this study, we set out to evaluate the antiobesity activities of our newly isolated Lacticaseibacillus paracasei LM-141 (LPLM141) using a high-fat diet (HFD)-fed rat model. Male Sprague-Dawley rats were fed with a HFD with or without low-dosage (2 × 107 CFU/day per rat) or high-dosage (2 × 109 CFU/day per rat) LPLM141 for 14 weeks. The results showed that administration of LPLM141 significantly decreased body weight gain, liver weight, adipose tissue weight, and epididymal white adipocyte size increased by HFD feeding. The abnormal serum lipid profile induced by HFD feeding was normalized by administration of LPLM141. The enhanced chronic low-grade inflammation in HFD-fed rats was reduced by LPLM141 supplementation, as reflected by decreased serum lipopolysaccharide (LPS) and monocyte chemoattractant protein-1 (MCP-1) levels, reduced macrophage infiltration in adipose tissue, and increased serum adiponectin concentration. In addition, the elevations of proinflammatory cytokine genes and suppression of PPAR-γ mRNA in adipose tissues of rats fed with a HFD were markedly reversed by LPLM141 administration. Oral administration of LPLM141 induced browning of epididymal white adipose tissue (eWAT) and activation of interscapular brown adipose tissue (iBAT) in rats fed with HFD. Consumption of LPLM141 exhibited a significant amelioration in insulin resistance, which were mechanistically caused by downregulation of the serum leptin level and upregulation of hepatic IRS-1 and p-Akt protein expressions, in HFD treated rats. LPLM141 consumption significantly decreased hepatic lipogenic gene expressions and preserved liver function stimulated by HFD treatment. Administration of LPLM141 obviously mitigated hepatic steatosis observed in HFD feeding rats. Our current findings shed light on LPLM141 supplementation that exhibited an antiobesity effect in HFD-fed rats by alleviating inflammation and insulin resistance, which further highlighted the potential of utilizing LPLM141 as a preventive/therapeutic probiotic agent for obesity.

36660595 Mononuclear phagocytic cells (MPCs) are classified into monocytes (Mos)/macrophages and dendritic cells (DCs) based on their functions. Cells of MPCs lineage act as immune modulators by affecting effector cells, such as NK cells, T cells, and B cells. This study aimed to investigate the effects of Lacticaseibacillus paracasei strain Shirota (LcS) ingestion on peripheral MPCs, particularly on their expression of functional cell-surface molecules enhanced in healthy adults. Thus, twelve healthy office workers consumed a fermented milk drink containing 1.0 × 1011 cfu of LcS (LcS-FM) or a control unfermented milk drink (CM) once a day for 6 weeks. Peripheral blood mononuclear cells (PBMCs) were prepared from blood samples, and immune cells and functional cell-surface molecules were analyzed. We observed remarkable differences in the expression of HLAABC, MICA, CD40, and GPR43 in plasmacytoid DCs (pDCs) between the LcS-FM and CM groups, whereas no difference was found in CD86 or HLADR expression. The LcS-FM group exhibited higher CD40 expression in both conventional DCs (cDCs) and Mos, especially in type 2 conventional DCs (cDC2s) and classical monocytes (cMos); higher percentages of cMos, intermediate monocytes (iMos), and nonclassical monocytes; and higher numbers of cMos and iMos in PBMCs than the CM group. LcS ingestion increased the expression of HLAABC, MICA, CD40, and GPR43 in pDCs and CD40 in cDCs and Mos, particularly cDC2s and cMos. These results suggest that LcS modulates the function of MPCs that may lead to the regulation of immune effector functions in healthy adults.

31464895 BACKGROUND: Lactobacillus paracasei and Glycyrrhiza glabra have been reported as having beneficial effects on Helicobacter pylori infection. We aimed to assess the efficacy and safety of fermented milk containing L paracasei HP7 and G glabra in patients with H pylori infection.

28199353 This study investigated allergy immunotherapy potential of Lactobacillus paracasei L9 to prevent or mitigate the particulate matter 2.5 (PM2.5) enhanced pre-existing asthma in mice. Firstly, we used a mouse model of asthma (a 21-day ovalbumin (OVA) sensitization and challenge model) followed by PM2.5 exposure twice on the same day of the last challenge. PM2.5 was collected from the urban area of Beijing and underwent analysis for metals and polycyclic aromatic hydrocarbon contents. The results showed that PM2.5 exposure enhanced airway hyper-responsiveness (AHR) and lead to a mixed Th2/ IL-17 response in asthmatic mice. Secondly, the PM2.5 exposed asthmatic mice were orally administered with L9 (4×107, 4×109 CFU/mouse, day) from the day of first sensitization to the endpoint, for 20 days, to investigate the potential mitigative effect of L9 on asthma. The results showed that L9 ameliorated PM2.5 exposure enhanced AHR with an approximate 50% decrease in total airway resistance response to methacholine (48 mg/ml). L9 also prevented the exacerbated eosinophil and neutrophil infiltration in bronchoalveolar lavage fluid (BALF), and decreased the serum level of total IgE and OVA-specific IgG1 by 0.44-fold and 0.3-fold, respectively. Additionally, cytokine production showed that L9 significantly decreased T-helper cell type 2 (Th2)-related cytokines (IL-4, -5, -13) and elevated levels of Th1 related IFN-γ in BALF. L9 also reduced the level of IL-17A and increased the level of TGF-β. Taken together, these results indicate that L9 may exert the anti-allergic benefit, possibly through rebalancing Th1/Th2 immune response and modulating IL-17 pro-inflammatory immune response. Thus, L9 is a promising candidate for preventing PM exposure enhanced pre-existing asthma.

34539604 Probiotic microorganisms may benefit the host by influencing diverse physiological processes, whose nature and underlying mechanisms are still largely unexplored. Animal models are a unique tool to understand the complexity of the interactions between probiotic microorganisms, the intestinal microbiota, and the host. In this regard, in this pilot study, we compared the effects of 5-day administration of three different probiotic bacterial strains (Bifidobacterium bifidum MIMBb23sg, Lactobacillus helveticus MIMLh5, and Lacticaseibacillus paracasei DG) on three distinct murine intestinal sites (ileum, cecum, and colon). All probiotics preferentially colonized the cecum and colon. In addition, probiotics reduced in the ileum and increased in the cecum and colon the relative abundance of numerous bacterial taxonomic units. MIMBb23sg and DG increased the inducible nitric oxide synthase (iNOS) in the ileum, which is involved in epithelial homeostasis. In addition, MIMBb23sg upregulated cytokine IL-10 in the ileum and downregulated the cyclooxygenase COX-2 in the colon, suggesting an anti-inflammatory/regulatory activity. MIMBb23sg significantly affected the expression of the main gene involved in serotonin synthesis (TPH1) and the gene coding for the serotonin reuptake protein (SERT) in the ileum and colon, suggesting a potential propulsive effect toward the distal part of the gut, whereas the impact of MIMLh5 and DG on serotonergic genes suggested an effect toward motility control. The three probiotics decreased the expression of the permeability marker zonulin in gut distal sites. This preliminary in vivo study demonstrated the safety of the tested probiotic strains and their common ability to modulate the intestinal microbiota. The probiotics affected host gene expression in a strain-specific manner. Notably, the observed effects in the gut were site dependent. This study provides a rationale for investigating the effects of probiotics on the serotonergic system, which is a topic still widely unexplored.

36079908 Commensal microorganisms in the human gut are a good source of candidate probiotics, particularly those with immunomodulatory effects that may improve health outcomes by regulating interactions between the gut microbiome and distal organs. Previously, we used an immune-based screening strategy to select two potential probiotic strains from infant feces in China, Bifidobacterium breve 207-1 (207-1) and Lacticaseibacillus paracasei 207-27 (207-27). In this study, the in vitro immunological effects and potential in vivo general health benefits of these two strains were evaluated using Lacticaseibacillus rhamnosus GG (LGG) as the control. The results showed that 207-1 and 207-27 significantly and differentially modulated the cytokine profiles of primary splenic cells, while did not induce abnormal systemic immune responses in healthy mice. They also modulated the gut microbiota composition in a strain-dependent manner, thus decreasing Gram-negative bacteria and increasing health-promoting taxa and short-chain fatty acid levels, particularly butyric acid. Conclusively, 207-1 and 207-27 shaped a robust gut environment in healthy mice in a strain-specific manner. Their potential immunomodulatory effects and other elite properties will be further explored using animal models of disease and subsequent clinical trials. This immune-based screening strategy is promising in efficiently and economically identifying elite candidate probiotics.

27754398 The most recent trend in research on probiotic bacteria aims at the exploitation of bioactive bacterial compounds that are responsible for health-promoting effects and suitable for medical applications. Therefore, the main purpose of this study was to ascertain if the immunomodulatory effects of L. paracasei strains on dendritic cells (DCs) were caused by bacterial metabolites released in the culture medium. For that reason, bacterial strains were grown in two media generally used for the culture of DCs, and the effects of culture filtrates on the maturation of DCs and cytokine production were evaluated. Moreover, to reveal potential synergistic effects on the immunomodulation of DCs, an artichoke phenolic extract (APE) was added to the media before bacterial growth. The experiments pointed out an interesting anti-inflammatory activity of a culture filtrate obtained after growing a probiotic L. paracasei strain in one of the media supplemented with APE. Therefore, this culture filtrate-which combines the anti-inflammatory activity and the other well-known health-promoting properties of artichoke phenolic compounds-could represent the basis for future particular exploitations.

30648597 Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) whose exact cause is still unclear. Disruption of the intestinal microflora is considered one of the main causes of the disease. Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) is a multifunctional strain that has been shown in previous studies to possess anti-inflammatory properties and to exert a modulatory effect on intestinal bacteria associated with certain pathogenic mechanisms of IBD. In the current study, we investigated the effects of NTU 101 on dextran sulfate sodium (DSS)-induced colitis in a mouse model. Colitis was induced in male C57BL/6 mice (total number n = 60) via dissolved DSS in drinking water on days 15-21 of the experiment. The effects of continuous 25 d feeding (days 0-25) of either a half or a full dose 2.3 × 109 colony-forming units (CFU)/kg body weight (BW)/d and 4.5 × 109 CFU/kg BW/d, respectively of NTU 101 was evaluated. Lactobacillus rhamnosus BCRC 16000 (BCRC 16000) and L. paracasei subsp. paracasei BCRC 14023 (BCRC 14023) strains were given to control groups. The results indicated that NTU 101 powder improved anti-oxidant capacity, reduced pro-inflammatory cytokine levels, increased anti-inflammatory cytokine levels, and slightly ameliorated body weight loss in DSS-treated mice during the final days of the study. This indicated that NTU 101 powder can relieve the clinical symptoms of DSS-induced colitis in mice.

29705500 OBJECTIVES: The beneficial effects of pro-, pre-, and synbiotics on obesity with insulin resistance have been reported previously. However, the strain-specific effect of probiotics and the combination with various types of prebiotic fiber yield controversial outcomes and limit clinical applications. Our previous study demonstrated that the probiotic Lactobacillus paracasei (L. paracasei) HII01, prebiotic xylooligosaccharide (XOS), and synbiotics share similar efficacy in attenuating cardiac mitochondrial dysfunction in obese-insulin resistant rats. Nonetheless, the roles of HII01 and XOS on gut dysbiosis and gut inflammation under obese-insulin resistant conditions have not yet, to our knowledge, been investigated. Our hypothesis was that pro-, pre-, and synbiotics improve the metabolic parameters in obese-insulin resistant rats by reducing gut dysbiosis and gut inflammation.

35874662 Hyperuricemia (HUA) is the presence of excessive uric acid (UA) in blood, which leads to an increased risk of chronic kidney disease and gout. Probiotics have the potential effect of alleviating HUA. The purpose of this study was to screen probiotics with UA-lowering activity and explore the underlying mechanism. The UA-lowering activity of 20 lactic acid bacteria strains was investigated in vitro, and the effect of candidate probiotics on UA metabolism was evaluated using the HUA Balb/c mouse model. The results showed that Lactobacillus paracasei X11 had excellent UA-lowering activity in vitro, which could degrade nucleotides and nucleosides completely within 30 min, and the degradation rates of purine and trioxypurine could reach 83.25% and 80.42%, respectively. In addition, oral administration of L. paracasei X11 could reduce serum UA by 52.45% and inhibit renal proinflammatory cytokine IL-1β by 50.69%, regulating adenosine deaminase (ADA), xanthine oxidase (XOD), and transporter expression (GLUT9, NPT1, and URAT1) to a normal level. Moreover, it could restore the ratio of Bacteroidetes to Firmicutes (Bac/Firm ratio) and showed a positive effect on the recovery of the intestinal microbiota. These findings provided fundamental information about the UA-lowering properties of probiotics, which suggested that L. paracasei X11 had the potential to be developed as a novel probiotic strain to ameliorate HUA.

35067214 Asthma is a chronic inflammatory disease related to the immune response of type 2 T helper cells (Th2), which affects all age groups. The incidence of asthma is increasing worldwide, and it has become a significant public health problem. This study aimed to investigate the immunomodulatory effects of Lacticaseibacillus (formerly Lactobacillus) paracasei K47 on mice with ovalbumin (OVA)-induced allergy. The consequences of orally administered heat-inactivated K47 in OVA-sensitised/challenged BALB/c mice were evaluated by assessing the serum levels of immunoglobulins (Igs), airway hyperresponsiveness (AHR), and bronchoalveolar lavage fluid (BALF) cytokine. In addition, the effect of K47 on type 1 T helper cells (Th1)/Th2 cytokine production in splenocytes from OVA-sensitised mice was evaluated. The results revealed that supplementation with K47 remarkably reduced serum levels of total IgE, OVA-specific IgE, and OVA-specific IgG1 in OVA-sensitised/challenged mice. In addition, K47 intervention ameliorated AHR and suppressed the accumulation of inflammatory cells in the BALF of OVA-sensitised/challenged mice. Furthermore, the immunomodulatory ability of K47 was mediated by regulation of the cytokine profile toward the Th1 response in the BALF, and splenocytes of OVA-sensitised mice. Taken together, these results suggested that K47 can modulate the host immune response to ameliorate AHR and inflammation in allergic asthma.

35744660 Mutualistic bacteria have different forms of interaction with the host. In contrast to the invasion of pathogenic bacteria, naturally occurring internalization of commensal bacteria has not been studied in depth. Three in vitro methods, gentamicin protection, flow cytometry and confocal laser scanning microscopy, have been implemented to accurately assess the internalization of two lactobacillus strains-Lacticaseibacillus paracasei BL23 and Lacticaseibacillus rhamnosus GG-in Caco-2 and T84 intestinal epithelial cells (IECs) under a variety of physiological conditions and with specific inhibitors. First and most interesting, internalization occurred at a variable rate that depends on the bacterial strain and IEC line, and the most efficient was BL23 internalization by T84 and, second, efficient internalization required active IEC proliferation, as it improved naturally at the early confluence stages and by stimulation with epidermal growth factor (EGF). IFN-γ is bound to innate immune responses and autolysis; this cytokine had a significant effect on internalization, as shown by flow cytometry, but increased internalization was not perceived in all conditions, possibly because it was also stimulating autolysis and, as a consequence, the viability of bacteria after uptake could be affected. Bacterial uptake required actin polymerization, as shown by cytochalasin D inhibition, and it was partially bound to clathrin and caveolin dependent endocytosis. It also showed partial inhibition by ML7 indicating the involvement of cholesterol lipid rafts and myosin light chain kinase (MLCK) activation, at least in the LGG uptake by Caco-2. Most interestingly, bacteria remained viable inside the IEC for as long as 72 h without damaging the epithelial cells, and paracellular transcytosis was observed. These results stressed the fact that internalization of commensal and mutualistic bacteria is a natural, nonpathogenic process that may be relevant in crosstalk processes between the intestinal populations and the host, and future studies could determine its connection to processes such as commensal tolerance, resilience of microbial populations or transorganic bacterial migration.

35485997 Colonization and development of gut microbiota during early life stage plays a key regulatory role in the establishment of the host-microbial relationship, which was conducive to progressing host immunity and maintaining health throughout the adulthood life span. This study was aimed to evaluate the protective effect from inflammatory bowel disease (IBD) in adulthood based on the early intervention of Lactobacillus paracasei N1115 (LP N1115). LP N1115 treatment was carried out during 2 weeks in postnatal mice. Then the dextran sodium sulphate (DSS)-induced colitis model mice were established in adulthood, and the status of intestinal tissues was detected. Results showed the decreased severity of intestinal tissue injury, cell apoptosis, and proinflammatory cytokines expression in DSS-induced model with LP N1115 early intervention. Therefore, the intake of LP N1115 in neonatal mice has played a long-term healthy role in the prevention of intestinal injury and inflammation in adulthood.

32483147 Mother's milk is the best choice for infants nutrition, however when it is not available or insufficient to satisfy the needs of the infant, formula is proposed as an effective substitute. Here, we report the results of a randomized controlled clinical trial (NCT03637894) designed to evaluate the effects of two different dietary regimens (standard formula and Lactobacillus paracasei CBA L74-fermented formula) versus breastfeeding (reference group) on immune defense mechanisms (primary endpoint: secretory IgA, antimicrobial peptides), the microbiota and its metabolome (secondary outcomes), in healthy full term infants according to the type of delivery (n = 13/group). We show that the fermented formula, safe and well tolerated, induces an increase in secretory IgA (but not in antimicrobial peptides) and reduces the diversity of the microbiota, similarly, but not as much as, breastmilk. Metabolome analysis allowed us to distinguish subjects based on their dietary regimen and mode of delivery. Together, these results suggest that a fermented formula favors the maturation of the immune system, microbiota and metabolome.

28654019 Background: Fermented foods have been proposed to prevent common infectious diseases (CIDs) in children attending day care or preschool.

29636018 BACKGROUND: The use of probiotics to improve anti-microbial defence, such as for influenza infections, is increasingly recommended. However, no data are available on the effect of probiotics on flu-associated secondary bacterial infections. There is strong evidence of a spatiotemporal association between influenza virus infection and invasive Neisseria meningitidis. We thus investigated the effect of feeding mice Lactobacillus paracasei CNCM I-1518 in a mouse model of sequential influenza-meningococcal infection.

37040355 Probiotics provide health benefits in various aspects and are believed to modulate the immune system by balancing gut microbiota homeostasis, termed the "microbiota-immune axis". Recent evidence supports that several Lactobacillus strains possess glucose-lowering and anti-inflammatory effects in an animal model of type 1 diabetes (T1D). Although probiotics of Lacticaseibacillus paracasei SD1 (SD1) and Lacticaseibacillus rhamnosus SD11 (SD11) exert human oral health benefits by reducing harmful bacterial populations, their clinical application regarding hypoglycemic-related traits as well as the underlying mechanisms are still lacking. In this report, we used multiple low doses of streptozotocin (STZ)-induced diabetic BALB/c mice to explore the effects of SD1 and SD11 supplementation on the regulation of markers related to T1D. Experimental mice were randomly assigned into five groups, non-STZ + V, STZ + V, STZ + SD1, STZ + SD11, and STZ + SDM (mixture of SD1 and SD11), and physiological data were measured every week. Blood and pancreas samples were collected at 4- and 8-weeks. Our results indicate that supplementation with SD1, SD11, or SDM for 8 weeks significantly improved body weights, glycemic levels, glucose tolerance, insulin levels, and lipid profiles. Probiotic administration also preserved islet integrity and increased β-cell mass in STZ-injected mice, as well as prevented infiltration of macrophages, CD4+, and CD8+ T cells into the islets. Significantly, SD1 and SD11 suppressed the levels of IL1-β, TNF-α and IFN-γ and increased IL-10, which is concomitant with the inhibition of cleaved caspase 3, caspase 9, caspase 8, proapoptotic Bax, NF-κBp65, pSTAT1, and iNOS. Additionally, the survival ability of β-cells was mediated by upregulated anti-apoptotic Bcl2. We conclude that SD1 and SD11 attenuate STZ-induced diabetic mice by stabilizing glycemic levels and reducing inflammation, thereby protecting β-cells. Among the probiotic treatment groups, SD11 revealed the best results in almost all parameters, indicating its potential use for alleviating hyperglycemia-associated symptoms.

33092151 The administration of a combination of probiotics and prebiotics is expected to be a promising strategy for improving irritable bowel syndrome (IBS) symptoms. This study aimed to investigate the efficacy of a synbiotic containing Lactobacillus paracasei and Opuntia humifusa extract for symptomatic improvement of IBS in a murine model and to evaluate the mechanism underlying the beneficial effects of this synbiotic. A total of 20 male Wistar rats aged 8 weeks with IBS induced by restraint stress were assigned into four groups and administered L. paracasei as a probiotic and O. humifusa extract as a prebiotic for 4 weeks. The primary outcome was stool consistency at week 4. To evaluate the mechanism underlying the beneficial effects of the synbiotic, fecal microbial analysis was conducted, and the serum corticosterone levels, tumor necrosis factor-α (TNF-α) levels in the colon tissue, and expression of tight junction proteins were investigated. All three treatment groups showed significantly lower scores for stool consistency than the control group at week 4 (all p < 0.001). When compared with the control group, the synbiotic groups showed a significantly greater abundance of L. paracasei in fecal microbial analysis, lower serum corticosterone levels, lower TNF-α levels in the colon tissue, and higher expression of tight junction proteins. This novel synbiotic containing L. paracasei and O. humifusa extract can improve the stool consistency in a murine model of IBS. It may be a promising treatment option for IBS, and human studies are warranted.

Assembly QC

Assembly Metric

Genome Characterization

Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System. anti-oxidative

Lipoteichoic Acid Is Involved in the Ability of the Immunobiotic Strain Lactobacillus plantarum CRL1506 to Modulate the Intestinal Antiviral Innate Immunity Triggered by TLR3 Activation. d-Alanylation of LTA

Lipoteichoic Acid Is Involved in the Ability of the Immunobiotic Strain Lactobacillus plantarum CRL1506 to Modulate the Intestinal Antiviral Innate Immunity Triggered by TLR3 Activation. d-Alanylation of LTA

Functional analysis of D-alanylation of lipoteichoic acid in the probiotic strain Lactobacillus rhamnosus GG. d-Alanylation of Teichoic Acid

Lipoteichoic Acid Is Involved in the Ability of the Immunobiotic Strain Lactobacillus plantarum CRL1506 to Modulate the Intestinal Antiviral Innate Immunity Triggered by TLR3 Activation. d-Alanylation of LTA

Exopolysaccharides from probiotic bacteria and their health potential. exopolysachharide gene

Exopolysaccharides from probiotic bacteria and their health potential. exopolysachharide gene

Exopolysaccharides from probiotic bacteria and their health potential. exopolysachharide gene

Towards a better understanding of Lactobacillus rhamnosus GG--host interactions. LTA glycosylation

Towards a better understanding of Lactobacillus rhamnosus GG--host interactions. LTA glycosylation

Towards a better understanding of Lactobacillus rhamnosus GG--host interactions. LTA glycosylation

Lipoteichoic acid is important in innate immune responses to gram-positive bacteria. lipoteichoic acid synthesis

Genes and molecules of lactobacilli supporting probiotic action. quorum sensing

Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System. anti-oxidative

Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System. anti-oxidative

Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System. anti-oxidative

Immunoreactive Proteins of Bifidobacterium longum ssp. longum CCM 7952 and Bifidobacterium longum ssp. longum CCDM 372 Identified by Gnotobiotic Mono-Colonized Mice Sera, Immune Rabbit Sera and Non-immune Human Sera. immunoreactive protein

Probiotics and immune health. stress-related proteins

Exploration of Survival Traits, Probiotic Determinants, Host Interactions, and Functional Evolution of Bifidobacterial Genomes Using Comparative Genomics. immunostimulatory oligodeoxynucleotides (ISS-ODNs), which are known to suppress IgE production and Th2 immune responses

Exported proteins in probiotic bacteria: adhesion to intestinal surfaces, host immunomodulation and molecular cross-talking with the host. retain the plasminogen at the bacterial surface in the form of aggregates, roles in the adhesion to intestinal surfaces or in bacterial–host interaction

Exported proteins in probiotic bacteria: adhesion to intestinal surfaces, host immunomodulation and molecular cross-talking with the host. binding with human fibronectin and plasminogen. , roles in the adhesion to intestinal surfaces or in bacterial–host interaction

Functional annotation of the genome unravels probiotic potential of Bacillus coagulans HS243. acid tolerance

Functional annotation of the genome unravels probiotic potential of Bacillus coagulans HS243. acid tolerance

Exported proteins in probiotic bacteria: adhesion to intestinal surfaces, host immunomodulation and molecular cross-talking with the host. retain the plasminogen at the bacterial surface in the form of aggregates, roles in the adhesion to intestinal surfaces or in bacterial–host interaction

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. Increase in IL-6, IL-1β and TNF-α

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. Immunomodulatory

GroEL of Lactobacillus johnsonii La1 (NCC 533) is cell surface associated: potential role in interactions with the host and the gastric pathogen Helicobacter pylori Bind to components of the gastrointestinal mucosa

Probiotic engineering: towards development of robust probiotic strains with enhanced functional properties and for targeted control of enteric pathogens. Improved thermotolerance (heat tolerance) of probiotic; increased solvent resistance by the probiotic strain

Lipoteichoic Acid Is Involved in the Ability of the Immunobiotic Strain Lactobacillus plantarum CRL1506 to Modulate the Intestinal Antiviral Innate Immunity Triggered by TLR3 Activation. tlr3 mediated immune response

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. polysaccharide production

Exploration of Survival Traits, Probiotic Determinants, Host Interactions, and Functional Evolution of Bifidobacterial Genomes Using Comparative Genomics. riggering Th17 immune response via an encrypted immunomodulatory peptide (“FAIVDEVDSILIDEAR”), YAIVDEVDSILIDEAR

Sortase-deficient lactobacilli: effect on immunomodulation and gut retention. lpxtg protein , ovalently couples a subset of extracellular proteins containing an LPXTG motif to the cell surface

Sortase-deficient lactobacilli: effect on immunomodulation and gut retention. extracellular proteins containing an LPXTG motif

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. increase il10

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. immunity protein

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. Increase in IL-10

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. immunity protein

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. immunity protein

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. immunity protein

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. immunity protein

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. immunity protein

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. Immunomodulatory

Probiotic-Based Bacteriocin: Immunity Supplementation Against Viruses. An Updated Review. Immunomodulatory

Immunomodulatory potential of four candidate probiotic Lactobacillus strains from plant and animal origin using comparative genomic analysis. Increase in phagocytosis and NO production

Lipoproteins Contribute to the Anti-inflammatory Capacity of Lactobacillus plantarum WCFS1. anti-inflammatory, interact with Toll-like receptor (TLR) 2

The structure of pyogenecin immunity protein, a novel bacteriocin-like immunity protein from Streptococcus pyogenes. Immunomodulatory

Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to the development of allergic asthma in childhood of mice cell-meditated immunity

Bypassing the Gut-Lung Axis via Microbial Metabolites: Implications for Chronic Respiratory Diseases. increases pool of TREG cells

Effects of Synbiotic Supplementation on Chronic Inflammation and the Gut Microbiota in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study. cytokine modulation

Consumption of Dairy Yogurt Containing Lactobacillus paracasei ssp. paracasei, Bifidobacterium animalis ssp. lactis and Heat-Treated Lactobacillus plantarum Improves Immune Function Including Natural Killer Cell Activity. cytokine modulation

Effect of synbiotic supplementation in children and adolescents with cystic fibrosis: a randomized controlled clinical trial. cytokine modulation

Selected commensal bacteria change profiles of Helicobacter pylori-induced T cells via dendritic cell modulation. cytokine modulation

Selected commensal bacteria change profiles of Helicobacter pylori-induced T cells via dendritic cell modulation. mucosal immunity

Irradiated Non-replicative Lactic Acid Bacteria Preserve Metabolic Activity While Exhibiting Diverse Immune Modulation. cytokine modulation

Exopolysaccharide Produced by Lactobacillus paracasei IJH-SONE68 Prevents and Improves the Picryl Chloride-Induced Contact Dermatitis. cytokine modulation

The molecular mechanisms of probiotic strains in improving ageing bone and muscle of d-galactose-induced ageing rats. cytokine modulation

Lactic acid bacterium, Lactobacillus paracasei KW3110, suppresses inflammatory stress-induced caspase-1 activation by promoting interleukin-10 production in mouse and human immune cells. cytokine modulation

Lactic acid bacterium, Lactobacillus paracasei KW3110, suppresses inflammatory stress-induced caspase-1 activation by promoting interleukin-10 production in mouse and human immune cells. Mucosal immune system

Lactic acid bacterium, Lactobacillus paracasei KW3110, suppresses inflammatory stress-induced caspase-1 activation by promoting interleukin-10 production in mouse and human immune cells. cytokine modulation, innate immunity

Lactic acid bacterium, Lactobacillus paracasei KW3110, suppresses inflammatory stress-induced caspase-1 activation by promoting interleukin-10 production in mouse and human immune cells. EGFR pathway

Immuno-physiological alterations from AFB1 in rats counteracted by treatments with Lactobacillus paracasei BEJ01 and montmorillonite clay mixture. cytokine modulation

Immunomodulatory effects and anti-Candida activity of lactobacilli in macrophages and in invertebrate model of Galleria mellonella. cytokine modulation

A Novel Rhamnose-Rich Hetero-exopolysaccharide Isolated from Lactobacillus paracasei DG Activates THP-1 Human Monocytic Cells. cytokine modulation

Lactobacillus delivery of bioactive interleukin-22. cytokine modulation

Lactobacillus paracasei KW3110 Prevents Blue Light-Induced Inflammation and Degeneration in the Retina. cytokine modulation

Lactobacillus paracasei KW3110 Prevents Blue Light-Induced Inflammation and Degeneration in the Retina. Mucosal immune system

Lactobacillus paracasei KW3110 Prevents Blue Light-Induced Inflammation and Degeneration in the Retina. cytokine modulation, innate immunity

A Potential Synbiotic Strategy for the Prevention of Type 2 Diabetes: Lactobacillus paracasei JY062 and Exopolysaccharide Isolated from Lactobacillus plantarum JY039. cytokine modulation

Lactobacillus paracasei L9 improves colitis by expanding butyrate-producing bacteria that inhibit the IL-6/STAT3 signaling pathway. cytokine modulation

Screening of immune-enhancing Lactobacillus in mice by using a cell-line. cytokine modulation

Exploring the potential of Lacticaseibacillus paracasei M11 on antidiabetic, anti-inflammatory, and ACE inhibitory effects of fermented dromedary camel milk (Camelus dromedaries) and the release of antidiabetic and anti-hypertensive peptides. cytokine modulation

Lactobacillus paracasei modulates the gut microbiota and improves inflammation in type 2 diabetic rats. cytokine modulation

Lacticaseibacillus paracasei GM-080 Ameliorates Allergic Airway Inflammation in Children with Allergic Rhinitis: From an Animal Model to a Double-Blind, Randomized, Placebo-Controlled Trial. cytokine modulation

Immunosuppressive Effects of Two Probiotics, Lactobacillus paracasei DSM 13434 and Lactobacillus plantarum DSM 15312, on CD4+ T Cells of Multiple Sclerosis Patients. cytokine modulation

Lactobacillus paracasei from koumiss ameliorates diarrhea in mice via tight junctions modulation. tight junction barrier

Lactobacillus paracasei from koumiss ameliorates diarrhea in mice via tight junctions modulation. gastro intestinal barrier

Direct effects of fermented cow's milk product with Lactobacillus paracasei CBA L74 on human enterocytes. tight junction barrier